Vatalanib (PTK-787; ZK222584; CGP79787) 2HCl

Alias: ZK 222584 (cpg-79787) 2HCl; ZK 222584; ZK222584; ZK-222584; PTK787; PTK 787; CGP 79787; CGP-797870; ZK-232934; PTK-787; ZK 232934; ZK232934; CGP79787D; PTK787/ZK 222584; CGP-7978
Cat No.:V0515 Purity: ≥98%
Vatalanib (PTK787 or ZK-222584, cpg-79787 2HCl) 2HCl is a novel, potent and orally bioavailable inhibitor of VEGFR2/KDR with potential anticancer activity.
Vatalanib (PTK-787; ZK222584; CGP79787) 2HCl Chemical Structure CAS No.: 212141-51-0
Product category: VEGFR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
500mg
1g
Other Sizes

Other Forms of Vatalanib (PTK-787; ZK222584; CGP79787) 2HCl:

  • Vatalanib (PTK-787; ZK-222584; CGP-79787)
  • Vatalanib succinate (PTK787 succinate; ZK-222584 succinate; CGP-79787 succinate)
Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Vatalanib (PTK787 or ZK-222584, cpg-79787 2HCl) 2HCl is a novel, potent and orally bioavailable inhibitor of VEGFR2/KDR with potential anticancer activity. In a cell-free experiment, it inhibits VEGFR2/KDR with an IC50 of 37 nM, is less effective against VEGFR1/Flt-1, and is 18-fold more potent against VEGFR3/Flt-4. With strong anti-proliferative activity in vitro and strong antitumor efficaciousness in vivo, it is an anilinophthalazine analog. The protein kinase domains of VEGFR 1 and 2 are bound by vatalanib, which then inhibits them. The PDGF receptor, c-Kit, and c-Fms are among the related receptor tyrosine kinases that this agent binds to and inhibits.

Biological Activity I Assay Protocols (From Reference)
Targets
VEGFR2/KDR (IC50 = 37 nM); VEGFR1/FLT1 (IC50 = 77 nM); VEGFR2/Flk1 (IC50 = 270 nM); PDGFRβ (IC50 = 580 nM); VEGFR3/FLT4 (IC50 = 660 μM)
ln Vitro

Vatalanib also inhibits PDGFRβ, Flk, and c-Kit, with IC50 values of 580 nM, 730 nM, and 270 nM, respectively. Additionally, at an IC50 of 7.1 nM, vatalanib inhibits the thymidine incorporation that VEGF induces in HUVECs. It also suppresses VEGF-induced migration and survival of endothelial cells in a dose-dependent manner within the same dose range, without having any cytotoxic or antiproliferative effects on cells that do not express VEGF receptors.[1] A recent study demonstrates that vatalanib increases the levels of the protein Bax and decreases Bcl-xL and Bcl-2, thereby significantly inhibiting the growth of hepatocellular carcinoma cells and enhancing the IFN/5-FU induced apoptosis.[2]

ln Vivo
Vatalanib results in dose-dependent suppression of the angiogenic response to VEGF and PDGF following a single oral dosage (25–100 mg/kg) in two models: one using growth factor implants, the other using tumor cell-driven angiogenesis. While having little effect on bone marrow leukocytes or circulating blood cells, vatalanib also inhibits the growth and metastases of a number of human carcinomas in nude mice within the same dose range. [1]
Enzyme Assay
In vitro kinase assays employ recombinant GST-fused kinase domains that are expressed in baculovirus and purified over glutathione-Sepharose. They are carried out as filter binding assays in 96-well plates. γ-[33P]ATP The phosphate donor in this scenario is ATP, while the acceptor is poly-(Glu:Tyr 4:1) peptide. Recombinant GST-fusion proteins are diluted, based on their specific activity, in 20 mM Tris·HCl (pH 7.5) containing 1-3 mM MnCl2, 3-10 mM MgCl2, 0.25 mg/mL polyethylene glycol 20000, and 1 mM DTT. The optimized buffer conditions for each GST-fused kinase include 20 mM Tris-HCl buffer (pH 7.5), 1-3 mM MnCl2, 3-10 mM MgCl2, 3-6 μg/mL poly-(Glu:Tyr 4:1), 0.25 mg/mL polyethylene glycol 20000, 8 μM ATP, 10 μM sodium vanadate, 1 mM DTT, and 0.2 μCi[γ-33P]ATP in a total volume of 30 μL, with or without a test substance. The incubation period lasts for 10 minutes at room temperature. Addition of 10 μL of 250 mM EDTA stops the reaction. The volume is divided in half (20 μL) and placed onto an Immobilon-polyvinylidene difluoride membrane using a 96-well filter system. After a thorough washing in 0.5% H3PO4, the membrane is submerged in ethanol. Following drying, the addition of Microscint cocktail and scintillation counting are carried out. In these as well as all the assays listed below, the IC50s for PTK787/ZK 222584 or SU5416 are determined using linear regression analysis of the percentage inhibition.
Cell Assay
An endothelial cell proliferation test based on BrdUrd incorporation is used to determine whether PTK787/ZK 222584 can inhibit a functional response to VEGF. Subconfluent HUVECs are seeded into 96-well plates that have been coated with 1.5% gelatin, and the plates are then incubated in growth medium at 37 °C with 5% CO2. The growth medium is changed after a day to basal medium that contains 1.5% FCS and a consistent amount of either VEGF (50 ng/mL), bFGF (0.5 ng/mL), or FCS (5%), with or without PTK787/ZK 222584. There are also wells without a growth factor included as a control. Prior to fixation, blocking, and the addition of peroxidase-labeled anti-BrdUrd antibody, cells are incubated for a further 24 hours after the addition of BrdUrd labeling solution. Using 3,3′5,5′-tetramethylbenzidine substrate, bound antibody is then identified. This reaction product is colored and can be measured spectrophotometrically at 450 nm.
Animal Protocol
The dorsal flank of C57/C6 mice is implanted subcutaneously with a porous Teflon chamber (volume: 0.5 mL) containing 0.8% w/v agar containing heparin (20 units/mL) with or without growth factor (3 μg/mL human VEGF, 2 μg/mL human PDGF). One day prior to chamber implantation and for five days following, the mice are given either vehicle (water) or Vatalanib (12.5, 25 or 50 mg/kg dihydrochloride p.o. once daily). The mice are put to death and the chambers are taken out at the conclusion of the treatment. The vascularized tissue encircling the chamber is carefully removed, weighed, and its hemoglobin content is measured to determine the amount of blood present.
References

[1]. Cancer Res . 2000 Apr 15;60(8):2178-89.

[2]. Ann Surg Oncol . 2011 Feb;18(2):589-96.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C20H15CLN4.2HCL
Molecular Weight
419.73
Exact Mass
346.10
Elemental Analysis
C, 57.23; H, 4.08; Cl, 25.34; N, 13.35
CAS #
212141-51-0
Appearance
White to off-white crystalline solid
SMILES
C1=CC=C2C(=C1)C(=NN=C2NC3=CC=C(C=C3)Cl)CC4=CC=NC=C4.Cl.Cl
InChi Key
AZUQEHCMDUSRLH-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H15ClN4.2ClH/c21-15-5-7-16(8-6-15)23-20-18-4-2-1-3-17(18)19(24-25-20)13-14-9-11-22-12-10-14;;/h1-12H,13H2,(H,23,25);2*1H
Chemical Name
N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine;dihydrochloride
Synonyms
ZK 222584 (cpg-79787) 2HCl; ZK 222584; ZK222584; ZK-222584; PTK787; PTK 787; CGP 79787; CGP-797870; ZK-232934; PTK-787; ZK 232934; ZK232934; CGP79787D; PTK787/ZK 222584; CGP-7978
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~85 mg/mL (~202.5 mM)
Water: ~10 mg/mL (~23.8 mM)
Ethanol: ~6 mg/mL (~14.3 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.3825 mL 11.9124 mL 23.8248 mL
5 mM 0.4765 mL 2.3825 mL 4.7650 mL
10 mM 0.2382 mL 1.1912 mL 2.3825 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
+
+
+

Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00268918 Completed Drug: Docetaxel
Drug: PTK787
Ovarian Cancer
Endometrial Cancer
Dana-Farber Cancer Institute September 2005 Phase 1
NCT00117299 Completed Drug: PTK787/ZK222584 Sarcoma University of Helsinki September 2004 Phase 2
NCT00056459 Completed Drug: Vatalanib Colorectal Neoplasms
Colonic Neoplasms
Novartis February 2003 Phase 3
NCT00056446 Completed Drug: Vatalanib Colorectal Neoplasms
Colonic Neoplasms
Novartis Pharmaceuticals January 2003 Phase 3
NCT00134355 Completed Drug: PTK787 Prostate Cancer University of Michigan Rogel
Cancer Center
July 2005 Phase 2
Biological Data
  • Vatalanib (PTK787) 2HCl

    Effects of PTK787/ZK 222584 on the growth of a xenograft of the human epithelial carcinoma A431, implanted s.c. in BALB/c nude mice. Cancer Res. 2000 Apr 15;60(8):2178-89.

  • Vatalanib (PTK787) 2HCl

    Effects of PTK787/ZK 222584 on the tensile strength of an incisional wound in rats. Cancer Res. 2000 Apr 15;60(8):2178-89.

  • Vatalanib (PTK787) 2HCl

    Effect of PTK787/ZK 222584 treatment with and after cyclophosphamide on blood cells in normal BALB/c mice. Cancer Res. 2000 Apr 15;60(8):2178-89.

Contact Us